On-chip integrated metasystem for spin-dependent multi-channel color holography.

On-chip integrated metasurface driven by in-plane guided waves is of great interests in various light-field manipulation applications such as colorful augmented reality and holographic display. However, it remains a challenge to design colorful multichannel holography by a single on-chip metasurface. Here we present metasurfaces integrated on top of a guided-wave photonic slab that achieves multi-channel colorful holographic light display. An end-to-end scheme is used to inverse design the metasurface for projecting off-chip preset multiple patterns. Particular examples are presented for customized patterns that were encoded into the metasurface with a single-cell meta-atom, working simultaneously at RGB color channels and for several different diffractive distances, with polarization dependence. Holographic images are generated at 18 independent channels with such a single-cell metasurface. The proposed design scheme is easy to implement, and the resulting device is viable for fabrication, promising plenty of applications in nanophotonics.

ICAM-1 may promote the loss of dopaminergic neurons by regulating inflammation in MPTP-induced Parkinson's disease mouse models.

Parkinson's disease (PD) is a chronic neurodegenerative disease with unclear pathogenesis that involves neuroinflammation and intestinal microbial dysbiosis. Intercellular adhesion molecule-1 (ICAM-1), an inflammatory marker, participates in neuroinflammation during dopaminergic neuronal damage. However, the explicit mechanisms of action of ICAM-1 in PD have not been elucidated. We established a subacute PD mouse model by the intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and observed motor symptoms and gastrointestinal dysfunction in mice. Immunofluorescence was used to examine the survival of dopaminergic neurons, expression of microglial and astrocyte markers, and intestinal tight junction-associated proteins. Then, we use 16 S rRNA sequencing to identify alterations in the microbiota. Our findings revealed that ICAM-1-specific antibody (Ab) treatment relieved behavioural defects, gastrointestinal dysfunction, and dopaminergic neuronal death in MPTP-induced PD mice. Further mechanistic investigations indicated that ICAM-1Ab might suppress neuroinflammation by inhibiting the activation of astrocytes and microglia in the substantia nigra and relieving colon barrier impairment and intestinal inflammation. Furthermore, 16 S rRNA sequencing revealed that the relative abundances of bacterial Firmicutes, Clostridia, and Lachnospiraceae were elevated in the PD mice. However, ICAM-1Ab treatment ameliorated the MPTP-induced disorders in the intestinal microbiota. Collectively, we concluded that the suppressing ICAM-1 might lead to the a significant decrease of inflammation and restore the gut microbial community, thus ameliorating the damage of DA neurons.

Pleiotropy of positive selection in ancient ACE2 suggests an alternative hypothesis for bat-specific adaptations to host coronaviruses.

Angiotensin-convertingenzyme 2 (ACE2) has dual functions, regulating cardiovascular physiology and serving as the receptor for coronaviruses. Bats, the only true flying mammals and natural viral reservoirs, have evolved positive alterations in traits related to both functions of ACE2. This suggests significant evolutionary changes in ACE2 during bat evolution. To test this hypothesis, we examine the selection pressure in ACE2 along the ancestral branch of all bats (AncBat-ACE2), where powered flight and bat-coronavirus coevolution occurred, and detect a positive selection signature. To assess the functional effects of positive selection, we resurrect AncBat-ACE2 and its mutant (AncBat-ACE2-mut) created by replacing the positively selected sites. Compared to AncBat-ACE2-mut, AncBat-ACE2 exhibits stronger enzymatic activity, enhances mice's performance in exercise fatigue, and shows lower affinity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Our findings indicate the functional pleiotropy of positive selection in the ancient ACE2 of bats, providing an alternative hypothesis for the evolutionary origin of bats' defense against coronaviruses.

Oxymatrine and Gut Microbiota Modulation: A Potential Therapeutic Strategy for Bone Cancer Pain Management.

Chronic pain often coincides with changes in gut microbiota composition. Yet, the role of gut microbiota in bone cancer pain(BCP) is still not fully understood. This study investigated the role of gut microbiota in BCP and the effect of oxymatrine(OMT) on gut microbiota in BCP. A BCP mice model was developed to assess gut microbiota composition, serum and brain tissue butyric acid levels, and blood-brain barrier(BBB) permeability. Microbiota transplantation was used to restore gut microbiota, and the effect of Clostridium butyricum (C. butyricum) or sodium butyrate(NaB) supplementation on pain-related behaviors and BBB integrity was evaluated. The potential benefits of OMT on gut microbiota composition, PPARγ/COX-2 signaling, BBB integrity, and pain-related behaviors were also explored. BCP significantly altered gut microbiota composition and reduced serum and brain tissue butyric acid levels. Additionally, BBB permeability increased considerably in the BCP group compared to sham and control mice. Microbiota transplantation, as well as C. butyricum or NaB supplementation, ameliorated pain-related behaviors and BBB integrity; the supplementation of C. butyricum or NaB boosted brain tight junction protein expression, potentially through modulating PPARγ/COX-2 signaling. OMT influenced gut microbiota composition and regulated PPARγ/COX-2 signaling in the BCP model, improving pain-related behaviors and BBB integrity. BCP affects gut microbiota composition and butyric acid levels. Modulating gut microbiota and butyric acid levels through transplantation or supplementation may alleviate BCP. OMT shows potential as a treatment by altering gut microbiota composition and regulating PPARγ/COX-2 signaling. These findings provide new insights into BCP pathophysiology and possible treatments. PERSPECTIVE: This study explores the impact of gut microbiota on bone cancer pain (BCP). Microbiota transplantation alleviates BCP and enhances BBB integrity. Also, Clostridium butyricum or sodium butyrate improves BBB via PPARγ/COX-2. Oxymatrine (OMT), a BCP treatment, modifies microbiota by regulating PPARγ/COX-2, in turn improving pain and BBB integrity. These findings suggest a therapeutic approach, emphasizing clinical relevance in targeting gut microbiota and restoring butyric acid levels.

Serum beta2-microglobulin acts as a biomarker for severity and prognosis in glioma patients: a preliminary clinical study.

BACKGROUND: Gliomas are the deadliest malignant tumors of the adult central nervous system. We previously discovered that beta2-microglobulin (B2M) is abnormally upregulated in glioma tissues and that it exerts a range of oncogenic effects. Besides its tissue presence, serum B2M levels serve as biomarkers for various diseases. This study aimed to explore whether serum B2M levels can be used in the diagnosis and prognosis of gliomas. METHODS: Medical records from 246 glioma patients were retrospectively analyzed. The relationship between preoperative serum B2M levels and clinicopathological features was examined. Kaplan-Meier analysis, alongside uni- and multivariate Cox regression, assessed the association between B2M levels, systemic inflammatory markers, and glioma patient prognosis. Receiver operating characteristic (ROC) curve analysis evaluated the diagnostic significance of these biomarkers specifically for glioblastoma (GBM). RESULTS: Patients with malignant gliomas exhibited elevated preoperative serum B2M levels. Glioma patients with high serum B2M levels experienced shorter survival times. Multivariate Cox analysis determined the relationship between B2M levels (hazard ratio = 1.92, 95% confidence interval: 1.05-3.50, P = 0.034) and the overall survival of glioma patients. B2M demonstrated superior discriminatory power in distinguishing between GBM and non-GBM compared to inflammation indicators. Moreover, postoperative serum B2M levels were lower than preoperative levels in the majority of glioma patients. CONCLUSIONS: High preoperative serum B2M levels correlated with malignant glioma and a poor prognosis. Serum B2M shows promise as a novel biomarker for predicting patient prognosis and reflecting the therapeutic response.

[Recent advances of molecular imprinting technology for the separation and recognition of complex biological sample systems].

Given continuous improvements in industrial production and living standards, the analysis and detection of complex biological sample systems has become increasingly important. Common complex biological samples include blood, serum, saliva, and urine. At present, the main methods used to separate and recognize target analytes in complex biological systems are electrophoresis, spectroscopy, and chromatography. However, because biological samples consist of complex components, they suffer from the matrix effect, which seriously affects the accuracy, sensitivity, and reliability of the selected separation analysis technique. In addition to the matrix effect, the detection of trace components is challenging because the content of the analyte in the sample is usually very low. Moreover, reasonable strategies for sample enrichment and signal amplification for easy analysis are lacking. In response to the various issues described above, researchers have focused their attention on immuno-affinity technology with the aim of achieving efficient sample separation based on the specific recognition effect between antigens and antibodies. Following a long period of development, this technology is now widely used in fields such as disease diagnosis, bioimaging, food testing, and recombinant protein purification. Common immuno-affinity technologies include solid-phase extraction (SPE) magnetic beads, affinity chromatography columns, and enzyme linked immunosorbent assay (ELISA) kits. Immuno-affinity techniques can successfully reduce or eliminate the matrix effect; however, their applications are limited by a number of disadvantages, such as high costs, tedious fabrication procedures, harsh operating conditions, and ligand leakage. Thus, developing an effective and reliable method that can address the matrix effect remains a challenging endeavor. Similar to the interactions between antigens and antibodies as well as enzymes and substrates, biomimetic molecularly imprinted polymers (MIPs) exhibit high specificity and affinity. Furthermore, compared with many other biomacromolecules such as antigens and aptamers, MIPs demonstrate higher stability, lower cost, and easier fabrication strategies, all of which are advantageous to their application. Therefore, molecular imprinting technology (MIT) is frequently used in SPE, chromatographic separation, and many other fields. With the development of MIT, researchers have engineered different types of imprinting strategies that can specifically extract the target analyte in complex biological samples while simultaneously avoiding the matrix effect. Some traditional separation technologies based on MIP technology have also been studied in depth; the most common of these technologies include stationary phases used for chromatography and adsorbents for SPE. Analytical methods that combine MIT with highly sensitive detection technologies have received wide interest in fields such as disease diagnosis and bioimaging. In this review, we highlight the new MIP strategies developed in recent years, and describe the applications of MIT-based separation analysis methods in fields including chromatographic separation, SPE, diagnosis, bioimaging, and proteomics. The drawbacks of these techniques as well as their future development prospects are also discussed.

[Determination of fatty acid composition after saponification of common oil pharmaceutical excipients by supercritical fluid-evaporative light scattering method and its application in oil identification].

Oils and fats are commonly used in the pharmaceutical industry as solvents, emulsifiers, wetting agents, and dispersants, and are an important category of pharmaceutical excipients. Fatty acids with unique compositions are important components of oil pharmaceutical excipients. The Chinese Pharmacopoeia provides clear descriptions of the fatty acid types and limits suitable for individual oil pharmaceutical excipient. An unqualified fatty acid composition or content may indicate adulteration or deterioration. The fatty acid composition, as a key indicator for the identification and adulteration evaluation of oil pharmaceutical excipients, can directly affect the quality and safety of oil pharmaceutical excipients and preparations. Gas chromatography is the most widely used technique for fatty acid analysis, but it generally requires derivatization, which affects quantitative accuracy. Supercritical fluid chromatography (SFC), an environmentally friendly technique with excellent separation capability, offers an efficient method for detecting fatty acids without derivatization. Unlike other chromatographic methods, SFC does not use nonvolatile solvents (e. g., water) as the mobile phase, rendering it compatible with an evaporative light-scattering detector (ELSD) for enhanced detection sensitivity. However, the fatty acids in oil pharmaceutical excipients exist in the free and bound forms, and the low content of free fatty acids in these oil pharmaceutical excipients not only poses challenges for their detection but also complicates the determination of characteristic fatty acid compositions and contents. Moreover, the compositions and ratios of fatty acids are influenced by environmental factors, leading to interconversion between their two forms. In this context, saponification provides a simpler and faster alternative to derivatization. Saponification degrades oils and fats by utilizing the reaction between esters and an alkaline solution, ultimately releasing the corresponding fatty acids. Because this method is more cost effective than derivatization, it is a suitable pretreatment method for the detection of fatty acids in oil pharmaceutical excipients using the SFC-ELSD approach. In this study, we employed SFC-ELSD to simultaneously determine six fatty acids, namely, myristic acid, palmitic acid, stearic acid, arachidic acid, docosanoic acid, and lignoceric acid, in oil pharmaceutical excipients. Saponification of the oil pharmaceutical excipients using sodium hydroxide methanol solution effectively avoided the bias in the determination of fatty acid species and contents caused by the interconversion of fatty acids and esters. The separation of the six fatty acids was achieved within 12 min, with good linearity within their respective mass concentration ranges. The limits of detection and quantification were 5-10 mg/L and 10-25 mg/L, respectively, and the spiked recoveries were 80.93%-111.66%. The method proved to be sensitive, reproducible, and stable, adequately meeting requirements for the analysis of fatty acids in oil pharmaceutical excipients. Finally, the analytical method was successfully applied to the determination of six fatty acids in five types of oil pharmaceutical excipients, namely, corn oil, soybean oil, coconut oil, olive oil, and peanut oil. It can be combined with principal component analysis to accurately differentiate different types of oil pharmaceutical excipients, providing technical support for the rapid identification and quality control of oil pharmaceutical excipients. Thus, the proposed method may potentially be applied to the analysis of complex systems adulterated with oil pharmaceutical excipients.

Microbiota regulates the TET1-mediated DNA hydroxymethylation program in innate lymphoid cell differentiation.

Innate lymphoid cell precursors (ILCPs) develop into distinct subsets of innate lymphoid cells (ILCs) with specific functions. The epigenetic program underlying the differentiation of ILCPs into ILC subsets remains poorly understood. Here, we reveal the genome-wide distribution and dynamics of the DNA methylation and hydroxymethylation in ILC subsets and their respective precursors. Additionally, we find that the DNA hydroxymethyltransferase TET1 suppresses ILC1 but not ILC2 or ILC3 differentiation. TET1 deficiency promotes ILC1 differentiation by inhibiting TGF-ß signaling. Throughout ILCP differentiation at postnatal stage, gut microbiota contributes to the downregulation of TET1 level. Microbiota decreases the level of cholic acid in the gut, impairs TET1 expression and suppresses DNA hydroxymethylation, ultimately resulting in an expansion of ILC1s. In adult mice, TET1 suppresses the hyperactivation of ILC1s to maintain intestinal homeostasis. Our findings provide insights into the microbiota-mediated epigenetic programming of ILCs, which links microbiota-DNA methylation crosstalk to ILC differentiation.

Injectable ultrasonic sensor for wireless monitoring of intracranial signals.

Direct and precise monitoring of intracranial physiology holds immense importance in delineating injuries, prognostication and averting disease1. Wired clinical instruments that use percutaneous leads are accurate but are susceptible to infection, patient mobility constraints and potential surgical complications during removal2. Wireless implantable devices provide greater operational freedom but include issues such as limited detection range, poor degradation and difficulty in size reduction in the human body3. Here we present an injectable, bioresorbable and wireless metastructured hydrogel (metagel) sensor for ultrasonic monitoring of intracranial signals. The metagel sensors are cubes 2 × 2 × 2 mm3 in size that encompass both biodegradable and stimulus-responsive hydrogels and periodically aligned air columns with a specific acoustic reflection spectrum. Implanted into intracranial space with a puncture needle, the metagel deforms in response to physiological environmental changes, causing peak frequency shifts of reflected ultrasound waves that can be wirelessly measured by an external ultrasound probe. The metagel sensor can independently detect intracranial pressure, temperature, pH and flow rate, realize a detection depth of 10 cm and almost fully degrade within 18 weeks. Animal experiments on rats and pigs indicate promising multiparametric sensing performances on a par with conventional non-resorbable wired clinical benchmarks.

Relationship between jejunum ATPase activity and antioxidant function on the growth performance, feed conversion efficiency, and jejunum microbiota in Hu sheep (Ovis aries).

BACKGROUND: ATPase activity and the antioxidant function of intestinal tissue can reflect intestinal cell metabolic activity and oxidative damage, which might be related to intestinal function. However, the specific influence of intestinal ATPase activity and antioxidant function on growth performance, feed conversion efficiency, and the intestinal microbiota in sheep remains unclear. RESULTS: This study analyzed the correlation between ATPase activity and antioxidant function in the jejunum of 92 Hu sheep and their growth performance and feed conversion efficiency. Additionally, individuals with the highest (H group) and lowest (L group) jejunum MDA content and Na+ K+-ATPase activity were further screened, and the effects of jejunum ATPase activity and MDA content on the morphology and microbial community of sheep intestines were analyzed. There was a significant correlation between jejunum ATPase and SOD activity and the initial weight of Hu sheep (P < 0.01). The H-MDA group exhibited significantly higher average daily gain (ADG) from 0 to 80 days old and higher body weight (BW) after 80 days. ATPase and SOD activities, and MDA levels correlated significantly and positively with heart weight. The jejunum crypt depth and circular muscle thickness in the H-ATP group were significantly higher than in the L-ATP group, and the villus length, crypt depth, and longitudinal muscle thickness in the H-MDA group were significantly higher than in the L-MDA group (P < 0.01). High ATPase activity and MDA content significantly reduced the jejunum microbial diversity, as indicated by the Chao1 index and observed species, and affected the relative abundance of specific taxa. Among species, the relative abundance of Olsenella umbonata was significantly higher in the H-MDA group than in the L-MDA group (P < 0.05), while Methanobrevibacter ruminantium abundance was significantly lower than in the L-MDA group (P < 0.05). In vitro culture experiments confirmed that MDA promoted the proliferation of Olsenella umbonata. Thus, ATPase and SOD activities in the jejunum tissues of Hu sheep are predominantly influenced by congenital factors, and lambs with higher birth weights exhibit lower Na+ K+-ATPase, Ca2+ Mg2+-ATPase, and SOD activities. CONCLUSIONS: The ATPase activity and antioxidant performance of intestinal tissue are closely related to growth performance, heart development, and intestinal tissue morphology. High ATPase activity and MDA content reduced the microbial diversity of intestinal tissue and affect the relative abundance of specific taxa, representing a potential interaction between the host and its intestinal microbiota.

Construction and validation of serum Metabolic Risk Score for early warning of malignancy in esophagus.

Using noninvasive biomarkers to identify high-risk individuals prior to endoscopic examination is crucial for optimization of screening strategies for esophageal squamous cell carcinoma (ESCC). We conducted a nested case-control study based on two community-based screening cohorts to evaluate the warning value of serum metabolites for esophageal malignancy. The serum samples were collected at enrollment when the cases had not been diagnosed. We identified 74 differential metabolites and two prominent perturbed metabolic pathways, and constructed Metabolic Risk Score (MRS) based on 22 selected metabolic predictors. The MRS generated an area under the receiver operating characteristics curve (AUC) of 0.815. The model performed well for the within-1-year interval (AUC: 0.868) and 1-to-5-year interval (AUC: 0.845) from blood draw to diagnosis, but showed limited ability in predicting long-term cases (>5 years). In summary, the MRS could serve as a potential early warning and risk stratification tool for establishing a precision strategy of ESCC screening.

Systematic evaluation of fMRI data-processing pipelines for consistent functional connectomics.

Functional interactions between brain regions can be viewed as a network, enabling neuroscientists to investigate brain function through network science. Here, we systematically evaluate 768 data-processing pipelines for network reconstruction from resting-state functional MRI, evaluating the effect of brain parcellation, connectivity definition, and global signal regression. Our criteria seek pipelines that minimise motion confounds and spurious test-retest discrepancies of network topology, while being sensitive to both inter-subject differences and experimental effects of interest. We reveal vast and systematic variability across pipelines' suitability for functional connectomics. Inappropriate choice of data-processing pipeline can produce results that are not only misleading, but systematically so, with the majority of pipelines failing at least one criterion. However, a set of optimal pipelines consistently satisfy all criteria across different datasets, spanning minutes, weeks, and months. We provide a full breakdown of each pipeline's performance across criteria and datasets, to inform future best practices in functional connectomics.

A novel non-invasive embryo evaluation method (NICS-Timelapse) with enhanced predictive precision and clinical impact.

The selection of the finest possible embryo in in-vitro fertilization (IVF) was crucial and revolutionary, particularly when just one embryo is transplanted to lessen the possibility of multiple pregnancies. However, practical usefulness of currently used methodologies may be constrained. Here, we established a novel non-invasive embryo evaluation method that combines non-invasive chromosomal screening (NICS) and Timelapse system along with artificial intelligence algorithms. With an area under the curve (AUC) of 0.94 and an accuracy of 0.88, the NICS-Timelapse model was able to predict blastocyst euploidy. The performance of the model was further evaluated using 75 patients in various clinical settings. The clinical pregnancy and live birth rates of embryos predicted by the NICS-Timelapse model, showing that embryos with higher euploid probabilities were associated with higher clinical pregnancy and live birth rates. These results demonstrated the NICS-Timelapse model's significantly wider application in clinical IVF due to its excellent accuracy and noninvasiveness.

Effect of regionalized structures on rock fracture process.

The structure of rocks plays a crucial role in their failure process. However, it is ignored that the interactions between rock internal structure and the effect of its own evolution on the rock fracture process. To investigate the effect between the evolution law of rock regionalized structures and their interaction relationships during failure. We conducted an experiment using visual acoustic imaging monitoring to study rock failure, introducing a new concept of characteristics of rock structure-regionalized structures. The findings reveal three main types of regionalized structures in rocks: skeleton regions, variable regions, and damage regions. These structures combine to form four categories of complex rock structures: block-type support skeletons, point column-type support skeletons, suspension-type weak support skeletons, and no skeletons. During the failure process, we found that these regionalized structures worked together synergistically to control rock failure. Although the evolutionary relationships among the structures show some similarities, the final fracture states vary significantly. Stress and strain distribution patterns clearly demonstrate that variations in the force capacities and roles of the regionalized structures influence the synergistic evolutionary relationships, ultimately impacting the mode of rock failure. This work provides new insights for further research on rock failure mechanisms and can significantly contribute to preventing rock engineering disasters related to regionalized structures.

Diabetes and aortic dissection: unraveling the role of 3-hydroxybutyrate through mendelian randomization.

BACKGROUND: In observational and experimental studies, diabetes has been reported as a protective factor for aortic dissection. 3-Hydroxybutyrate, a key constituent of ketone bodies, has been found to favor improvements in cardiovascular disease. However, whether the protective effect of diabetes on aortic dissection is mediated by 3-hydroxybutyrate is unclear. We aimed to investigate the causal effects of diabetes on the risk of aortic dissection and the mediating role of 3-hydroxybutyrate in them through two-step Mendelian randomization. MATERIALS AND METHODS: We performed a two-step Mendelian randomization to investigate the causal connections between diabetes, 3-hydroxybutyrate, and aortic dissection and calculate the mediating effect of 3-hydroxybutyrate. Publicly accessible data for Type 1 diabetes, Type 2 diabetes, dissection of aorta and 3-hydroxybutyrate were obtained from genome-wide association studies. The association between Type 1 diabetes and dissection of aorta, the association between Type 2 diabetes and dissection of aorta, and mediation effect of 3-hydroxybutyrate were carried out separately. RESULTS: The IVW method showed that Type 1 diabetes was negatively associated with the risk of aortic dissection (OR 0.912, 95% CI 0.836-0.995), The weighted median, simple mode and weighted mode method showed consistent results. The mediated proportion of 3-hydroxybutyrate on the relationship between Type 1 diabetes and dissection of aorta was 24.80% (95% CI 5.12-44.47%). The IVW method showed that Type 2 diabetes was negatively associated with the risk of aortic dissection (OR 0.763, 95% CI 0.607-0.960), The weighted median, simple mode and weighted mode method showed consistent results. 3-Hydroxybutyrate does not have causal mediation effect on the relationship between Type 2 diabetes and dissection of aorta. CONCLUSION: Mendelian randomization study revealed diabetes as a protective factor for dissection of aorta. The protective effect of type 1 diabetes on aortic dissection was partially mediated by 3-hydroxybutyrate, but type 2 diabetes was not 3-hydroxybutyrate mediated.

A Method for Detecting Five Carbapenemases in Bacteria Based on CRISPR-Cas12a Multiple RPA Rapid Detection Technology.

Introduction: As the last line of defense for clinical treatment, Carbapenem antibiotics are increasingly challenged by multi-drug resistant bacteria containing carbapenemases. The rapid spread of these multidrug-resistant bacteria is the greatest threat to severe global health problems. Methods: To solve the problem of rapid transmission of this multidrug-resistant bacteria, we have developed a rapid detection technology using CRPSPR-Cas12a gene editing based on multiple Recombinase polymerase amplification. This technical method can directly isolate the genes of carbapenemase-containing bacteria from samples, with a relatively short detection time of 30 minutes. The instrument used for the detection is relatively inexpensive. Only a water bath can complete the entire experiment of Recombinase polymerase amplification and trans cleavage. This reaction requires no lid during the entire process while reducing a large amount of aerosol pollution. Results: The detection sensitivity of this method is 1.5 CFU/mL, and the specificity is 100%. Discussion: This multi-scene detection method is suitable for screening populations in wild low-resource environments and large-scale indoor crowds. It can be widely used in hospital infection control and prevention and to provide theoretical insights for clinical diagnosis and treatment.

Predictors of Inadequate Serum Urate Response to Low-Dose Febuxostat in Male Patients with Gout.

Objective: This study aimed to understand predictors of inadequate response (IR) to low-dose febuxostat treatment based on clinical variables. Methods: We pooled data from 340 patients of an observational cohort and two clinical trials who received febuxostat 20 mg/day for at least 3 months. IR was defined as failure to reach the target serum urate level (sUA<6 mg/dL) at any time point during 3 months treatment. The potential predictors associated with short- or mid-term febuxostat IR after pooling the three cohorts were explored using mixed-effect logistic analysis. Machine learning models were performed to evaluate the predictors for IR using the pooled data as the discovery set and validated in an external test set. Results: Of the 340 patients, 68.9% and 51.8% were non-responders to low-dose febuxostat during short- and mid-term follow-up, respectively. Serum urate and triglyceride (TG) levels were significantly associated with febuxostat IR, but were also selected as significant features by LASSO analysis combined with age, BMI, and C-reactive protein (CRP). These five features in combination, using the best-performing stochastic gradient descent classifier, achieved an area under the receiver operating characteristic curve of 0.873 (95% CI [0.763, 0.942]) and 0.706 (95% CI [0.636, 0.727]) in the internal and external test sets, respectively, to predict febuxostat IR. Conclusion: Response to low-dose febuxostat is associated with early sUA improvement in individual patients, as well as patient age, BMI, and levels of TG and CRP.

Preparation of porous polylactic acid nanofibers and application in non-electret high-efficiency filtration composites.

Air pollution caused by fine particulate matter (PM0.3) has drawn increasing attention as an overwhelming threat to public health. Electret treatment is commonly used to improve the filtration performance of commercial fibrous filter materials by enhancing the electrostatic adsorption effect, but it is greatly affected by environmental factors (especially humidity). Moreover, filter materials are generally non-degradable and non-recyclable, causing serious environmental pollution. Herein, a strategy to manufacture fully degradable polylactic acid (PLA) filtration composites based on porous PLA nanofibers prepared by electrospinning was investigated in this study. Porous, bead-on-string and conventional PLA nanofibers could be obtained by adjusting spinning condition parameters. The porous PLA nanofibers exhibited 9.8 times greater specific surface area (24.01 m2 g-1) and 18 times more cumulative pore volume (0.108 cm3 g-1) than conventional PLA nanofibers. More importantly, fibrous filtration composites based on porous PLA nanofibers possessed a high PM0.3 filtration efficiency (99.9989%), low pressure drop (90.35 Pa) and high air permeability (72.4 Pa-1) at an air flow rate of 32 L min-1 without electret treatment. The fibrous filtration composites based on conventional or bead-on-string PLA nanofibers also exhibited excellent filtration performance (>99.99%), but the associated high pressure drop and low air permeability limited their application.

Transcutaneous auricular vagal nerve stimulation for consciousness recovery in patients with prolonged disorders of consciousness (TAVREC): study protocol for a multicenter, triple-blind, randomized controlled trial in China.

INTRODUCTION: Prolonged disorders of consciousness (pDoC) are a catastrophic condition following brain injury with few therapeutic options. Transcutaneous auricular vagal nerve stimulation (taVNS), a safe, non-invasive intervention modulating thalamo-cortical connectivity and brain function, is a possible treatment option of pDoC. We developed a protocol for a randomised controlled study to evaluate the effectiveness of taVNS on consciousness recovery in patients with pDoC (TAVREC). METHODS AND ANALYSIS: The TAVREC programme is a multicentre, triple-blind, randomised controlled trial with 4 weeks intervention followed by 4 weeks follow-up period. A minimum number of 116 eligible pDoC patients will be recruited and randomly receive either: (1) conventional therapy plus taVNS (30 s monophasic square current of pulse width 300 µs, frequency of 25 Hz and intensity of 1 mA followed by 30 s rest, 60 min, two times per day, for 4 weeks); or (2) conventional therapy plus taVNS placebo. Primary outcome of TAVREC is the rate of improved consciousness level based on the Coma Recovery Scale-Revised (CRS-R) at week 4. Secondary outcomes are CRS-R total and subscale scores, Glasgow Coma Scale score, Full Outline of UnResponsiveness score, ECG parameters, brainstem auditory evoked potential, upper somatosensory evoked potential, neuroimaging parameters from positron emission tomography/functional MRI, serum biomarkers associated with consciousness level and adverse events. ETHICS AND DISSEMINATION: This study was reviewed and approved by the Research Ethics Committee of the First Affiliated Hospital of Nanjing Medical University (Reference number: 2023-SR-392). Findings will be disseminated in a peer-reviewed journal and presented at relevant conferences. TRIAL REGISTRATION NUMBER: ChiCTR2300073950.

MicroRNA bmo-miR-31-5p inhibits apoptosis and promotes BmNPV proliferation by targeting the CYP9e2 gene of Bombyx mori.

BACKGROUND: Bombyx mori nuclear polyhedrosis virus (BmNPV), as a typical baculovirus, is the primary pathogen that infects the silkworm B. mori, a lepidopteran species. Owing to the high biological safety of BmNPV in infecting insects, it is commonly utilized as a biological insecticide for pest control. Apoptosis is important in the interaction between the host and pathogenic microorganisms. MicroRNAs (miRNAs) influence immune responses and promote stability of the immune system via apoptosis. Therefore, the study of apoptosis-related miRNA in silkworms during virus infection can not only provide support for standardizing the prevention and control of diseases and insect pests, but also reduce the economic losses to sericulture caused by the misuse of biological pesticides. RESULTS: Through transcriptome sequencing, we identified a miRNA, miR-31-5p, and demonstrated that it can inhibit apoptosis in silkworm cells and promote the proliferation of BmNPV in BmE-SWU1 cells. We identified a target gene of miR-31-5p, B. mori cytochrome P450 9e2 (BmCYP9e2), and demonstrated that it can promote apoptosis in silkworm cells and inhibit the proliferation of BmNPV. Moreover, we constructed transgenic silkworm strains with miR-31-5p knockout and confirmed that they can inhibit the proliferation of BmNPV. CONCLUSION: These data indicate that miR-31-5p may exert functions of inhibiting apoptosis and promoting virus proliferation by regulating BmCYP9e2. The findings demonstrate how miRNAs influence host cell apoptosis and how they are involved in the host immune system response to viruses, providing important insights into the applications of biological insecticides for pest control. © 2024 Society of Chemical Industry.